NM_020932.3:c.59C>A

Variant names:

• chrX-76427989-C-A
• rs782197127
• NM_020932.3:c.59C>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_020932.3(MAGEE1):​c.59C>A​(p.Ala20Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000879 in 1,205,510 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 35 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A20V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000071 (0 hom., 0 hem., cov: 25)
  • Exomes 𝑓: 0.000090 (0 hom. 35 hem.)
• Consequence: MAGEE1 NM_020932.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.98
• Publications: 2 publications found

Genes affected

MAGEE1 (HGNC:24934): (MAGE family member E1) This gene encodes an alpha-dystrobrevin-associated MAGE (melanoma-associated antigen) protein, which is a member of the MAGE family. The protein contains a nuclear localization signal in the N-terminus, 30 12-amino acid repeats beginning at nt 60 with the consensus sequence ASEGPSTSVLPT, and two MAGE domains in the C-terminus. It may play a signaling role in brain, muscle, and peripheral nerve. This gene is located on X chromosome in a region containing loci linked to cognitive disability. [provided by RefSeq, Mar 2010]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.03658077).
• BS2: High Hemizygotes in GnomAdExome4 at 35 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020932.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGEE1	NM_020932.3	MANE Select	c.59C>A	p.Ala20Glu	missense	Exon 1 of 1	NP_065983.1	Q9HCI5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGEE1	ENST00000361470.4	TSL:6 MANE Select	c.59C>A	p.Ala20Glu	missense	Exon 1 of 1	ENSP00000354912.2	Q9HCI5

Frequencies

GnomAD3 genomes AF: 0.0000708 AC: 8 AN: 112929 Hom.: 0 Cov.: 25

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000150

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000239 AC: 4 AN: 167372 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000546

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000897 AC: 98 AN: 1092581 Hom.: 0 Cov.: 32 AF XY: 0.0000975 AC XY: 35 AN XY: 359065

African (AFR) AF: 0.00 AC: 0 AN: 26340

American (AMR) AF: 0.00 AC: 0 AN: 34600

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19169

East Asian (EAS) AF: 0.00 AC: 0 AN: 30083

South Asian (SAS) AF: 0.00 AC: 0 AN: 53162

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39658

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3772

European-Non Finnish (NFE) AF: 0.000110 AC: 92 AN: 839999

Other (OTH) AF: 0.000131 AC: 6 AN: 45798

GnomAD4 genome AF: 0.0000708 AC: 8 AN: 112929 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 35079

African (AFR) AF: 0.00 AC: 0 AN: 31103

American (AMR) AF: 0.00 AC: 0 AN: 10780

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2659

East Asian (EAS) AF: 0.00 AC: 0 AN: 3561

South Asian (SAS) AF: 0.00 AC: 0 AN: 2778

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6263

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 238

European-Non Finnish (NFE) AF: 0.000150 AC: 8 AN: 53349

Other (OTH) AF: 0.00 AC: 0 AN: 1517

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000416

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000346 AC: 1

ExAC AF: 0.0000330 AC: 4

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-1.1
CADD	Benign	12
DANN	Benign	0.89
DEOGEN2	Benign	0.0051	T
FATHMM_MKL	Benign	0.055	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.037	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.81	L
PhyloP100		-2.0
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-0.15	N
REVEL	Benign	0.026
Sift	Benign	0.44	T
Sift4G	Benign	0.94	T
Polyphen		0.0020	B
Vest4		0.12
MVP		0.043
MPC		0.37
ClinPred		0.015	T
GERP RS		-2.8
PromoterAI		-0.091	Neutral
Varity_R		0.066
gMVP		0.36
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs782197127; hg19: chrX-75648382;